9-35089051-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032634.4(PIGO):c.*41T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,612,920 control chromosomes in the GnomAD database, including 802,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 73974 hom., cov: 31)

Exomes 𝑓: 1.0 ( 728129 hom. )

Consequence

PIGO
NM_032634.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.254

Publications

11 publications found

Variant links:

Genes affected

PIGO (HGNC:23215): (phosphatidylinositol glycan anchor biosynthesis class O) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This protein is involved in the transfer of ethanolaminephosphate (EtNP) to the third mannose in GPI. At least three alternatively spliced transcripts encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

PIGO Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hyperphosphatasia with intellectual disability syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia
hyperphosphatasia-intellectual disability syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PIGO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 9-35089051-A-C is Benign according to our data. Variant chr9-35089051-A-C is described in ClinVar as [Benign]. Clinvar id is 366751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PIGO	NM_032634.4 link	c.*41T>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000378617.4	NP_116023.2	Q8TEQ8-1
PIGO	NM_001201484.2 link	c.*41T>G	3_prime_UTR_variant	Exon 13 of 13		NP_001188413.1	Q8TEQ8-2
PIGO	NM_152850.4 link	c.*41T>G	3_prime_UTR_variant	Exon 12 of 12		NP_690577.2	Q8TEQ8-2
PIGO	XM_005251619.4 link	c.*41T>G	3_prime_UTR_variant	Exon 11 of 11		XP_005251676.1	Q8TEQ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGO	ENST00000378617.4 link	c.*41T>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_032634.4	ENSP00000367880.3		Q8TEQ8-1

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

149945

AN:

152136

Hom.:

73918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.951

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.986

GnomAD2 exomes

AF:

0.996

AC:

249629

AN:

250640

AF XY:

0.997

show subpopulations

Gnomad AFR exome

AF:

0.948

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.998

AC:

1458423

AN:

1460666

Hom.:

728129

Cov.:

AF XY:

0.999

AC XY:

725642

AN XY:

726616

show subpopulations

African (AFR)

AF:

0.949

AC:

31756

AN:

33462

American (AMR)

AF:

0.996

AC:

44517

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26081

AN:

26082

East Asian (EAS)

AF:

1.00

AC:

39692

AN:

39692

South Asian (SAS)

AF:

1.00

AC:

86034

AN:

86040

European-Finnish (FIN)

AF:

1.00

AC:

53326

AN:

53336

Middle Eastern (MID)

AF:

0.997

AC:

5370

AN:

5388

European-Non Finnish (NFE)

AF:

1.00

AC:

1111516

AN:

1111644

Other (OTH)

AF:

0.997

AC:

60131

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

120

239

359

478

598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.986

AC:

150060

AN:

152254

Hom.:

73974

Cov.:

AF XY:

0.986

AC XY:

73390

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.951

AC:

39505

AN:

41524

American (AMR)

AF:

0.991

AC:

15170

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5176

AN:

5176

South Asian (SAS)

AF:

1.00

AC:

4821

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10612

AN:

10612

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68021

AN:

68032

Other (OTH)

AF:

0.986

AC:

2077

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.995

Hom.:

91768

Bravo

AF:

0.984

Asia WGS

AF:

0.996

AC:

3465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hyperphosphatasia with intellectual disability syndrome 2

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.0

(source)

DANN

Benign

0.61

PhyloP100

0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-35089051-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over